A Small Biopharma That Doesn't Use CROs

By Ed Miseta, Chief Editor, Clinical Leader
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When it comes to conducting clinical trials, most emerging companies choose to access external resources through partnering with CROs. That is what makes the clinical trial approach of Context Therapeutics so different. CEO Martin Lehr does not use CROs, preferring instead to take part in investigator-sponsored trials (ISTs). An IST is a trial that is initiated and managed by researchers from a non-pharmaceutical entity, such as an individual investigator, institution, or cooperative group.

"The genesis of this strategy goes back to my venture days at Osage University Partners,” says Lehr. “Investment firms are focused on generating returns for their institutional backers in as short a time frame as possible. Most investors believe that CROs provide the most efficient path to delivering high-quality data, fast. Investigator-sponsored trials are generally looked down upon.”

According to Lehr, ISTs have a reputation for poor enrollment, limited data capture, poor data quality, and bias. Data ownership and control over publications are perceived as further complications. However, times and assumptions change.

“There seemed to be a disconnect,” says Lehr. “I was taught that ISTs were looked down upon and produced data that other investors would not trust or value. Yet I was getting one email blast after another from highly ranked analysts who were telling investors to attend IST presentations that were likely to move individual public stocks or the entire biotech index. To me, that was a clear sign that the market does value ISTs in a much more positive manner than venture investors.”

He wondered if his own company was to go down the path of an investigator sponsor trial, how might he do it? What are the things that he should look out for? And what are the benefits and pitfalls of these trials?

A LARGE COST-SAVINGS

The first thing Lehr learned about ISTs was related to cost. If you run an oncology trial with a CRO, which Context had done in the past, the costs are quite high. That is true whether the trial is conducted in the U.S., Europe, or even Asia. Lehr notes that a Phase 2 trial for a small molecule oncology therapy can cost up to $200,000 per patient when working with a CRO. In contrast, IST per-patient costs ranged between $8,000 and $14,000 per patient. Lehr wondered where this signifi- cant cost difference came from.

“Companies pay a premium to CROs for the ability to work with professionals who know what they are doing and to work with an organization that has the scale to deliver,” he says.

When a company wants to run large, randomized clinical trials that require dozens of clinical sites, a CRO is almost always the right choice to operationalize the trial. However, Lehr argues that in the case of small to midsize Phase 2 trials where safety has clearly been established in Phase 1, CROs might not be the best option for emerging biopharmas.

Both academic centers and CROs have fixed overhead, to some degree, which leads to redundancies in clinical trial management. For example, it is common in CRO-led trials to have project managers from the company, CRO, and academic center. That redundancy is essential for quality control in large Phase 3 trials but is not always necessary for Phase 2 studies. Through direct interaction with the academic site, ISTs have fewer redundancies, which helps lower their cost.

In addition, an IST is a partnership versus a CRO-driven trial which is fee-for-service. An IST is truly an academic research project; therefore, the costs associated with the trial, from an institutional overhead standpoint, are significantly lower.

“Running an IST is a way for universities to differentiate themselves and provide their patient network with proprietary access to clinical trials. Doing so also helps grow the size and reputation of the institution.”

Regarding bias in the study, Lehr recommends you avoid trials with a single site, single primary investigator, and small number of patients. He instead suggests opening multiple sites, including those that may not be even associated with the institution. Doing so will eliminate the potential for bias — real or perceived — in the study.

ONE MAJOR TRADE-OFF

The major benefits of an IST are the cost-savings and the gravitas the institutional partner brings to the program. According to Lehr, the biggest negative is the control that must be given up. Legally and contractually, the university will become the study sponsor. That means the investigator will either file their own IND or cross-reference an IND that already had been filed with the FDA by the company.

“It is 100 percent their trial,” cautions Lehr. “We have rights to the data produced, but they’re able to publish and present the data. As the company granting access to your drug and/or providing financial support to the trial, you are engaging in a trade. The university is a partner performing a scientific exercise and is not a service provider.”

The cost-savings easily trump the loss of control over the trial, but there is another benefit that Lehr later became aware of. If a startup is not backed by one of the top VC funds, it’s hard for investors, the public, and clinicians to know if your company has a good product and whether it is running smart, well-designed clinical trials. Hiring a respected and well-known CRO is great, but all that tells anyone is that you have the cash to pay a CRO; that doesn’t actually add any significance to the trial.

“If we run a large trial in partnership with Memorial Sloan Kettering under an IST, that says something about our product,” says Lehr. “Investigators at Memorial Sloan Kettering are in a privileged position of having the pick of the litter of clinical trials to lead. When academic centers choose to work with us, it provides a quantitative qualifier for external parties. This model gives us enormous scale and reach in a very capital-efficient manner.”

Partnering with a well-regarded academic center extends beyond the trial. For the investigator and the academic center, it benefits them to publicize the trial to enhance enrollment and bring awareness to the clinical trial expertise of the institution. From a communications standpoint, the academic center and the company are in alignment. Some centers even prefer to lead communications, which greatly helps the emerging company because the communications team at a large institution has a higher probability of positioning the trial in top media outlets.

VET YOUR PARTNER

To select a CRO partner for a clinical trial, companies typically send out an RFP followed by a rigorous vetting process prior to final selection. Lehr notes that just like CROs, you must also vet your potential academic center partners. How many trials in your therapeutic area has that institution performed in the last five years? How many patients have they treated and are in their patient network? How many doctors do they have with the required expertise?

“That gives you a much better sense of the size, scope, and reach of the institution,” says Lehr. “I would also want to know if they have any competing trials.”

Thus far, the IST model is working well for Context. The company has two ISTs of its lead candidate Onapristone ER enrolling and three more that will be initiated in the next six months. Eventually there will be around 300 patients enrolled in these trials.

If a drug was early in the development cycle with limited information about the compound’s safety and efficacy, there could be more risk involved in turning it over to an academic researcher. “This is certainly not a one-size-fits-all approach,” adds Lehr. “It may not work for everyone, but it works very well for our pipeline and our company. If a drug is well-tolerated, we see very moderate risk in allowing an institution like Memorial Sloan Kettering to run the trial.”